Although HIV-1 and HIV-2 share 40-60% homology at the nucleotide level, the pathogenesis of the viral infections are fairly divergent. Again, HTLV-II and HIV-1 are both T cell tropic viruses that replicate very differently in their target cells, the former causing the host to become transformed and the latter having a marked cytopathic effect. Specific viral determinants may govern the different pathogenicities of these viruses in their host cells. We have initiated studies involving the construction of recombinant viruses that have a single gene replacement of a given virus type. Target sequences that are currently being investigated are in the LTR, tat, rev, env, and integrase genes. These recombinants viruses will be transfected into the host cell and the effects of these substitutions on viral replication will be studied.